title: From simple bacterial and archaeal replicons to replication N/U-domains.
abstract: The Replicon Theory proposed 50 years ago has proven to apply for replicons of the three domains of life. Here, we review our knowledge of genome organization into single and multiple replicons in bacteria, archaea and eukarya. Bacterial and archaeal replicator/initiator systems are quite specific and efficient, whereas eukaryotic replicons show degenerate specificity and efficiency, allowing for complex regulation of origin firing time. We expand on recent evidence that ~50% of the human genome is organized as ~1,500 megabase-sized replication domains with a characteristic parabolic (U-shaped) replication timing profile and linear (N-shaped) gradient of replication fork polarity. These N/U-domains correspond to self-interacting segments of the chromatin fiber bordered by open chromatin zones and replicate by cascades of origin firing initiating at their borders and propagating to their center, possibly by fork-stimulated initiation. The conserved occurrence of this replication pattern in the germline of mammals has resulted over evolutionary times in the formation of megabase-sized domains with an N-shaped nucleotide compositional skew profile due to replication-associated mutational asymmetries. Overall, these results reveal an evolutionarily conserved but developmentally plastic organization of replication that is driving mammalian genome evolution.
authors.affiliation: Ecole Normale Supérieure, IBENS UMR8197 U1024, Paris 75005, France. Electronic address: hyrien@biologie.ens.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hyrien
authors.forename: Aurélien
authors.initials: A
authors.lastname: Rappailles
authors.forename: Guillaume
authors.initials: G
authors.lastname: Guilbaud
authors.forename: Antoine
authors.initials: A
authors.lastname: Baker
authors.forename: Chun-Long
authors.initials: CL
authors.lastname: Chen
authors.forename: Arach
authors.initials: A
authors.lastname: Goldar
authors.forename: Nataliya
authors.initials: N
authors.lastname: Petryk
authors.forename: Malik
authors.initials: M
authors.lastname: Kahli
authors.forename: Emilie
authors.initials: E
authors.lastname: Ma
authors.forename: Yves
authors.initials: Y
authors.lastname: d'Aubenton-Carafa
authors.forename: Benjamin
authors.initials: B
authors.lastname: Audit
authors.forename: Claude
authors.initials: C
authors.lastname: Thermes
authors.forename: Alain
authors.initials: A
authors.lastname: Arneodo
mesh_terms: D000818:Animals; D001105:Archaea / Q000235:genetics*; D001419:Bacteria / Q000235:genetics*; D004261:DNA Replication; D056890:Eukaryota / Q000235:genetics*; D016678:Genome; D042822:Genomic Instability; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008322:Mammals; D008967:Molecular Biology / Q000266:history / Q000639:trends; D012093:Replicon
keywords: CTR; DH; TTR; cascade model; constant timing region; double hexamer; nucleotide compositional skew; replication fork polarity; replication origins; replication timing; timing transition region